The present invention relates to novel derivatives of psoralen. It concerns more particularly monofunctional derivatives of psoralen consisting of pyrido (3,4-c)-psoralens. The invention also relates to the obtention of such compounds. The invention is also concerned with the use of such compounds in cosmetology, namely for stimulating pigmentation of the skin and as pharmaceuticals, in particular, for the treatment of skin diseases. The invention also relates to cosmetic and pharmaceutical compositions containing such compounds as their active ingredient.
Photochemical therapy which relies on the activation of photoactive molecules of the furocouramin family, namely psoralens, on human skin by ultraviolet A radiations is rapidly developing in dermatology. It is indeed a particularly effective and convenient therapeutic technique for the treatment of benign, chronic dermatoses such as psoriasis which affects 2-3% of the population of the world, and for the treatment of malignant dermatoses such as mycosis fungoides, malignant cutaneous lymphoma, which is rare but has a particularly severe development. This therapeutic treatment has also been employed with a certain amount of success in the treatment of numerous chronic inflammatory skin diseases such a atypical eczema, lichen planus, parapsoriasis guttata, pruritis of the hemodialysed beings and in photodermatoses and depigmentation diseases such as vitiligo.
The preparation of certain psoralen derivatives and the use thereof for the treatment of skin afflictions, particularly psoriasis, has already been proposed. A reference illustrating the prior art in this field is French patent publication No. 2,405,067 for pharmaceutical compositions containing monofunctional derivatives of psoralen for the treatment of skin afflictions. This patent publication, to which reference may be had if necessary, sets out in a detailed manner knowledge at that time relative to derivatives of psoralen and their use as pharmaceuticals.
Briefly, psoralens are used in association with ultraviolet light in phototherapy for skin diseases such as psoriasis. This treatment is known as PUVA therapy. Recent studies have, however, shown that certain bifunctional psoralens such as 8-methoxypsoralen, known by its abbreviation 8-MOP and 5-methoxypsoralen, abbreviation 5-MOP, are carcinogenic in mice after exposure to light in the near ultraviolet range around 365 nm. On the contrary, 3-carbethoxypsoralen which is a monofunctional derivative of psoralen is completely safe from this point of view, while having a therapeutic activity in respect to patients having psoriasis.
The psoralens currently used in therapy such as 8-methoxypsoralen or 5-methoxypsoralen are agents capable of forming cross-links in the DNA, which cross-links are difficult to repair and capable of introducing errors in genetic replication. This property doubtless explains their high mutagenic activity and carcinogenesis in animals. They are therefore effective medicines but propably not devoid of risk for continual use on human beings. This is why photochemical therapy is prohibited for youths up to the age of 18-20 years and one tries to use it as little as possible before the age of 50.
In cosmetology, products are also known which stimulate pigmentation and are comprised of a derivatives of psoralen such as 5-methoxy psoralen (or 5-MOP). They find applications in cosmetic compositions for tanning skin and/or protection of skin against the sun. The drawback with such products is that they are mutagenic.